System and method of using ultrafast raman spectroscopy and a laser for quasi-real time detection and eradication of pathogens

ABSTRACT

Resonance Raman scatter is used to differentiate in quasi-real time (QRT) surfaces bearing pathogens from adjacent pathogen-free surface regions. The fingerprint generated from pathogens on a selected surface by a 1 second pulse of 532 nm emission for approximately one second is collected and is relayed by fiber-optic to a computerized controller that determines whether the target selected surface is contaminated by pathogens or is pathogen-free. If contaminated the pathogens are eradicated by UVC radiation. This is performed by a pattern of Resonance Raman diagnostic emission and diagnostic sensor fibers. The data received by the computer is examined instantly, and should the site be diagnosed as contaminated with pathogens, UVC radiation is repeated immediately and repeated until the selected surface is read as being pathogen-free.

CROSS-REFERENCE TO RELATED APPLICATION

This application is a divisional application of U.S. application Ser.No. 16/854,022 filed on Apr. 21, 2020, that claimed priority ofProvisional Patent Application 62/920,468 filed on May 2, 2019, all ofwhich are incorporated herein in their entirety by reference.

BACKGROUND OF THE INVENTION 1. Field of the Invention

The present invention is generally directed to devices that analyzeorganic and micro-organic tissue by detecting spectra, and linking thosedevices to a modality for the quasi-real-time (QRT) concurrent diagnosisand eradication of pathogens.

2. Description of the Prior Art

Surgical excision of neoplastic tumor tissue, as well as other anomaloustissues, has historically been performed manually using steel blades aswell as lasers etc. In recent years, robotic devices have been used toassist the surgeon. By way of example, many surgeons advocate the use ofthe Mohs technique to diagnose malignant tissues of the skin. The Mohstechnique includes mapping a specimen of the target tissue, staining thetissue and evaluating the tissue under a microscope to determine theamount and location of residual tumor cells. The area in question ismarked for orientation and local anesthetic is used. The tissue issurgically removed in layers, divided and mapped with reference pointson the patient and upon the slides of the frozen sections. Thesesections are analyzed histopathologically and if any area of thespecimen contains anomalous tissue, the marks guide the surgeon to theprecise location or locations to determine if anomalous tissue stillexists. The process is then repeated until no tumor is seen on any ofthe subsequent surgical specimens. There are many disadvantages to thistreatment system. There may be unnecessary tissue removal and cosmeticdamage. Long treatment sessions may occur due to the manual microscopicviewing and assessment of each layer removed. Freezing the tissuesamples may also be required which decreases the accuracy of theresults. A simpler, more efficient, more accurate, and less timeconsuming method of diagnosis and removal of the abnormal tissue wouldrepresent a significant advance in patient care. Kittrell¹, Redd² andBeckman³. All recognized the potential of Raman Spectroscopy as a methodfor differentiating anomalous from adjacent normal tissue. However, thetime required for normal Raman to perform this task was too long to makeit practical as a driver for an ablative energy to be used. Kircher andHarmson⁴ has suggested injection of nanoparticles to selectively tag thetumor cells which requires the injection of toxic or potentially toxicsubstances into the body. Fox, Beckman⁵ have shown that high-powered CO2laser energy impinging on cancerous and normal tissues does not disturbthe ability of Raman to differentiate them. And recently C. Liu, Alfano,Beckman et al have shown that a variety of ultrafast Raman designatedResonance Raman⁶ and Zhou⁷ could perform differentiation of basal cellcarcinoma from adjacent normal tissue in one second or less, makingquasi-real-time (QRT) feasible as a driver for a therapeutic entity suchas, but not limited to a high-powered carbon dioxide laser for the firsttime⁸. This feasibility, with the methodology utilized to ensure theability to selectively remove anomalous tissue with clear tumor freemargins, and create a computerized template of the removal site in orderto facilitate cosmetic repair of the margin, is the subject of thisapplication. ¹ References 1-4² Reference 5³ Reference 6⁴ References7-10⁵ Reference 20⁶ Reference 15⁷ Reference 19⁸ Reference 21

SUMMARY OF THE INVENTION

The invention is directed to a system and method for detecting pathogenson surfaces and eradicating them in real-time.

A medical device for diagnosing and eliminating or compromising organicmicro-organisms, including viruses (collectively “pathogens”), on aselected surface comprising a first source for directing excitationradiation at a selected surface to produce resonance Raman scattering(RRS) representative of the pathogens; a second source for directing UVCradiation at the selected surface to destroy or compromise detectedpathogens; detecting means for detecting Raman scatter at said selectedsurface when excitation radiation impinges on the pathogens; determiningmeans for determining whether said detected Raman scatter is indicativeof the presence of a pathogen sought to be destroyed or compromised;activation means for activating said second source for directing UVCradiation at the pathogens issuing said Raman scatter to destroy orcompromise the pathogens only when these are determined to be thepathogens sought to be destroyed or compromised.

A device for detecting and eradicating pathogens on a selected surfacecomprising:

a first source for directing an array of excitation radiation at aselected surface to produce resonance Raman scattering (RRS);

a second source for directing an array of UVC radiation at the selectedsurface to irradiate pathogens at the selected surface;

fiber optic or waveguide light conduits arranged in a pattern to deliversaid array of excitation radiation and said array of UVC radiation tothe selected surface target site;

detecting means for detecting said RRS at said target site whenexcitation radiation impinges on the selected surface; and

determining means for determining whether said detected RRS isindicative of the presence of the pathogen on the selected surface; and

activation means for activating said second source to direct the arrayof UVC radiation at the selected surface to irradiate the selectedsurface only when the selected surface is determined to support orexhibit the pathogen to create a peripheral pathogen-free zonecircumscribing pathogens at the selected surface target site.

A method of diagnosing and eradicating pathogens comprising the steps of

directing an array of excitation radiation at a selected surface targetsite with fiber optic or waveguide light conduits arranged in a patternto produce resonance Raman resonance RRS at said target site whenexcitation radiation impinges on the selected surface; and;

directing an array of UVC radiation at the selected surface target sitewith fiberoptic or waveguide light conduits arranged in a pattern todestroy or compromise pathogens on the selected surface; detecting saidRSS at said target site when excitation radiation impinges on theselected surface; and

determining whether said detected RRS is indicative of the presence ofpathogens,

whereby directing UVC eradication radiation at the selected surfacetarget site to eradicate the pathogens at said selected surface at thetarget site is performed only when the selected surface target site isdetermined to exhibit pathogen to create a peripheral pathogen-free zonecircumscribing a pathogen-free region at the selected surface targetsite.

A medical device for detecting and diagnosing organic micro-organisms,including viruses (collectively “pathogens”), on a selected surfacecomprising a source for directing excitation radiation at a selectedsurface to produce resonance Raman scattering (RRS) representative ofthe pathogens; detecting means for detecting Raman scatter at saidselected surface when excitation radiation impinges on the pathogens;and

determining means for determining whether said detected Raman scatter isindicative of the presence of a pathogen sought to be diagnosed.

BRIEF DESCRIPTION OF THE DRAWINGS

The following descriptions are in reference to the accompanying drawingsin which the same or similar parts are referenced by the same numeralsthroughout the several drawings, and wherein:

FIG. 1 is Part 1 of a schematic of one embodiment of the medical devicefor diagnosing and treating anomalous tissue as disclosed herein,illustrating the sequencing from the energy sources to the impact site,and is continued in FIG. 2;

FIG. 2 is Part 2 of the schematic of the embodiment shown in FIG. 1,starting from the plume at the impact site and following the path of theRaman scatter through the devices necessary for the diagnosis andtreatment of the anomalous tissue as disclosed herein;

FIG. 3 is a flow chart detailing the logical functions during the usageof the medical device embodied in FIGS. 1 and 2;

FIG. 4 depicts the rasterized image formed by an array forming device ofa diagnostic array at the site of laser treatment by either a probe orconfocal microscopic projection of the energies and demonstrates the useof two different patterns of coaxial exciter/sensor display and trackingpatterns to delineate anomalous tissue and remove it while creating aclear tissue zone around the lesion;

FIG. 5 is a schematic of two-dimensional array as it is represented in acomputer/controller;

FIG. 6 is a schematic of a three-dimensional array as it is representedin a computer/controller;

FIG. 7 schematically depicts the path of a robotically or manuallycontrolled display with diagnosis and ablation resulting in a 300 Micronzone clear of anomalous tissue;

FIG. 8 illustrates two tracking patterns of the arrays: one to debulkthe anomalous tissue from the outside in, and the other to create aperimeter outlining the lesion from the inside out;

FIGS. 9a and 9b depict a fingerprint taken from a basal cell carcinomaspecimen and from an adjacent specimen of normal tissue, both withResonance Raman 532 nm energy in a 1.0 second pulse;

FIG. 10a is a schematic of the energies going through the arrayproducing device into a confocal microscope creating a Raman scatterplume picked up by the sensors into the sensor device;

FIG. 10b is an enlarged view of the region A in FIG. 10 a;

FIG. 11 is a schematic representation of the probe carrying therapeuticand diagnostic energy coaxially to the target site, resulting inResonance Raman scatter input to the sensor after aberrant scatter hasbeen filtered out; and

FIG. 12 is a rendition of the energy paths taken in the production of adiagnostic/therapeutic event, with emphasis on the creation of arraysand patterns.

DETAILED DESCRIPTION OF THE EMBODIMENTS OF THE INVENTION

In the various figures like reference numbers refer to identical orsimilar like parts. The figures are exemplary and are not drawn toscale.

As seen in FIGS. 1 and 2 a preferred embodiment of the medical device 10is shown for diagnosing and treating anomalous tissue. The medicaldevice 10 comprises a high energy source 20T (therapeutic) such as butnot limited to a High Peak powered CO2 laser, and a low energy source20D (diagnostic) energy source such as, but not limited to 532 micronenergy.

These energy sources are either under either the control of a manualcontroller 150, or a robotic display controller 110 send energy, in thisembodiment, coaxially through conduit 25 DT through filter 820 to thearray producing device 30 after stray energy 825 has been filtered out.The arrays formed and shown in FIGS. 4, 5, 7 and 8 continue throughconduit 35 DTA to either the probe 40 or confocal microscope 50. Thesignals in the conduit 35DTA are focused by either delivery device 40,50 onto the target site by a focusing lens or system of lenses 60. Theablative energy creates a plume 75 containing Resonance Raman scatter aswell some aberrant therapeutic scatter and diagnostic scatter, which isfiltered out by lenses 335/345. Pure Resonance Raman energy is thentransmitted through conduit 85 to the sensors 80 which relays it inconduit 95 to the spectrometer 90 where the array is represented as inFIG. 5. Conduit 105 conveys it to the computer 100 where the fingerprintFIG. 9 is received and a determination is made as to whether the siteanalyzed is anomalous or normal. Should the fingerprint be anomalous,the surgeon under manual control 150 or the robotic controller 110triggers a pulse of ablative energy 20T On to the target site 70. If itis determined that the tissue is normal, then the surgeon under manualcontrol at 150 or the robotic controller at 110 either sends anotherpulse deeper into the same site, or the site is moved to an adjacentarea and the sequence repeated. In either case the sequence is repeateduntil all anomalous tissue is removed using a pattern, by example, asshown in FIG. 8.

As used herein, the term “anomalous” or “anomaly” refers to that tissuethat it is desirable to be removed. The anomalous tissue can be, forexample, cancerous or precancerous lesions, or abnormalities such asatheromata, viruses and other pathologies. If a determination is made bythe computer database 100 that the fingerprint of the target tissue 70is anomalous, the controller 110 activates the energy source 20T and thesite is ablated

On the visualized tissue 120 the target site 70 is selected and thediagnostic energy source 20D is triggered sending energy through filter820 on to the array producing device 30. A surgeon can determine whetherthe array of diagnostic energy is directed either to the probe 40 orconfocal microscope 50. From there the radiation is directed through thefocusing lens 60 onto the target site 70 where is produces a plume 75containing the Resonance Raman scatter as well as some spurious orforeign scatter. The foreign scatter Is filtered out by filters 335 and345 and the pure Resonance Raman energy 85 is captured by the sensor 80and relayed through conduit 95 to the spectrometer 90 from which it isinput through conduit 105 to the computer data base 100 where afingerprint of the energy is produced. Should the site be found to beanomalous a message is sent through the manual controller 150 or therobotic display controller 110 triggering a therapeutic pulse of energyfrom source 20T resulting in an ablation of the tissue site 70.

As used herein, an anomalous fingerprint can be a malignant fingerprintnot yet ablated or an anomalous site that has been ablated but not yetrid of abnormality.

The energy source 20T delivers ablative energy to that same tissue sitethrough the probe 40 or the microscope 50 sufficient to ablate at leasta portion of the target tissue site 70. This therapeutic ablative energy20T may be delivered in one or multiple doses as desired or required.The number, the power, and duration of the pulses may be adjusted asrequired to ablate the anomalous tissue. As used herein, the term“ablate” refers to effectively removing the anomalous tissue byseparation, destruction, vaporization, evaporation, melting, geneticmodification or the like.

In another embodiment a combined energy source 20DT can be used toreplace separate energy sources 20D and 20T to deliver both thediagnostic and the excitation beam and the therapeutic beam. Such energysource may be, for example but not limited to a frequency doubled Nd:YAGlaser emitting 532 nm energy, with suitable power configurations such asbut not limited to continuous wave, pulsed high peak power lasers, femtosecond lasers and other electromagnetic energy forms. Energy sources arenot limited to light sources such as lasers and can be any otherelectromagnetic source known to those skilled in the art that issufficient to achieve the results desired. One or more lenses can beused to focus the therapeutic laser energy at the target tissue to beablated.

If it is determined that the fingerprint 105 of the target tissue 70 isnormal the procedure can proceed differently depending on the requiredresult. The array of either the probe 40 or the microscope 50 can bemoved to the next location. The subsequent target site may be deeper atthe same site or to an adjacent site. The procedure is illustrated bythe flow chart shown in FIG. 3.

Utilizing the patterns formed by the arrays depicted in FIGS. 5, 6, 7,and 8, the direction of the excitation, the Resonance Raman scatter, andablative beam as necessary will be relayed after fingerprintinterpretation to the robotic display controller 110 and the appropriatelocation correction for the target site 70 made. All the arrays notedabove are designed in a manner that creates by way of example, at leasta 300μ region of contiguous free anomalous tissue sites in the samehorizontal or depth path as seen in FIG. 7. Thus, a zone at least 300μwide free of anomalous tissue will be created in 3-D multiple passes atdifferent depths until all anomalous tissue is removed.

It may be necessary to diagnose remaining target tissue 70 after thetherapeutic ablation or to diagnose tissue below a tissue layer. Adecision can then be made by the robotic display controller 110 or thesurgeon to deliver ablative energy to the same target tissue 70 ratherthan move to another anatomical location. If this decision is made, thearray may remain on the target tissue 70 and the controller 110 orsurgeon will trigger the diagnostic energy source 20D to ablate thetissue even though it has a normal fingerprint in it.

The diagnostic ablation can be done, for example to diagnose ananomalous tissue lying beneath the normal tissue. This step isparticularly important when diagnosing and treating at the edges ofabnormal masses to ensure the entire abnormality is removed. During thisprocedure, for example, the fingerprint of the denatured tissue is usedto determine normalcy or normalcy based on tissue that has been ablatedone or more times. For example, with basal cell carcinomas the malignantlesion can be hidden by normal tissue on the surface while malignanttissue is growing underneath. Some anomalous tissue may be known to beentirely under one or more layers of normal tissue requiring the normaltissue first to be removed to access the anomalous tissue. Afterablating the normal target tissue 70, the medical device may thenproceed to diagnose adjacent normal tissue. As used herein, normaltarget tissue can be normal tissue or denatured normal tissue. As noted,whether to move to a new target tissue site or ablate the normal tissuecan be decided by the surgeon before or during treatment and can also bedetermined by the surgeon before ordering treatment. It is contemplatedthat the robotic controller 110 can be programmed with specificdimensions or with a specific sequence of steps described above. Anon-limiting example of a programmed event is the continueddiagnosis/treatment until reaching a non-limiting 300 micron anomaloustissue free zone 200 as shown in array of FIG. 7. A non-limiting exampleof a specific sequence might be repeating the therapeutic sequence threetimes after anomalous fingerprints and before performing anotherdiagnosis. Any combination of diagnosis and therapeutic and diagnosticablation therapy can be programmed into the controller 110 and used byone skilled in the surgical art. It is also contemplated that thesurgeon can determine the necessary sequences during treatment oroverride programmed sequences as required. Alternatively, a triggeringdevice within or connected to the controller 110 can initiate thenecessary sequence based on preprogrammed information.

The display monitor 130 shown in FIG. 2 can be utilized for severaloptions. Non-limiting examples of its uses included viewing thefingerprints, displaying the operating parameters, providing real-timeinformation as to the duration of treatment, or patient information. Itmay also be in some instances used by the surgeon to manipulate theprobe, or the joystick of the manually operated microscopic display aswell as viewing the procedure as being performed robotically with orwithout input from the remote super database 140.

The probe 40 or the microscopic array of confocal microscope 50 ofdevice 10 can be manually driven by the surgeon during treatment to theanomalous tissue with or use of the monitor 130. Due to the small-scaleprecise nature of the treatment the arrays of the probe 40 or microscope50 can also be robotically driven. For example, a robot or rasteringmechanism can be utilized and driven by 110 to precisely control thelocation of the array. During the treatment process the robot mechanismcan also be, for example, an articulated robotic arm. Alternatively, therobotic device can be an optical scanner raster. These robotic devicesare provided by way of example and not limitation, and other roboticapparatuses known in the art can be used to control the movement of thearrays.

In one embodiment the probe 40 can be configured to almost contact thetarget tissue. This may require a disposable clear lens (not shown)capping the distal end of the probe preventing debris from absorbing theenergies. A lens such as this may be appropriate for the distal lenssystem of the microscopic delivery system. Protective windows could bemade of quartz (fused silica). Sapphire or any other suitable material,and should be easily removable and easily cleaned or replaced asdesired.

In another embodiment the probe 40 can also contain an inert gascatheter (not shown) that can deliver positive pressure of air,nitrogen, or other gas through a lumen at the distal end of the probe 70or through an inert gas catheter that can protect the environment andthe probe tip from debris. As used herein, the “plume” is any materialresulting from the ablation of the tissue such as Raman scatter 75, aplume of smoke, blood, ablative tissue remains, and other fluids.Provision for irrigation of the tissue site as well as known aspirationprovisions by vacuum with attached collecting chamber are contemplatedbut not shown.

Another embodiment would have a combined excitation/ablation/scatterdetection path in the same fibers 35DTA as seen. In order to accommodatethis coaxial orientation a dichroic beam splitter is used to combine theoptical paths. The wavelength of the exciter emission and therapeuticemission would to be the same, and by way of example only, could be 532nm emission such as produced by frequency doubled Nd:YAG lasers and blueor KTP (potassium titanyl phosphate lasers. Resonance Raman diagnosticemission would be pulses of approximately but not limited to 7 mW ofpower while therapeutic power would be high peak power pulses with powersuch as but not limited to 1000 Watts.

In another embodiment, the surgical microscope such as, but not limitedto, a Zeiss OPM1 6 could be modified to accept all of the conduits andtheir variations as outlined in the above probe embodiments, whereinenergy from the diagnostic exciter source 20D, and 20T therapeuticsource could be merged into arrays such as seen in FIGS. 4, 5, and 7,passing through appropriate filters and focus onto the target site.Provision could be made for manual joystick operation of the beam aswell as robotic control. Sensor/collector fibers at the distal end wouldbe parfocal with the projected exciter/therapeutic arrays.

In another embodiment, all of fibers excitation, therapeutic, andsensor/collector fibers could be between but not limited to 10 to 350μfrom the tissue. In another embodiment, therapeutic energy could beparfocal and focused on the exciter/sensor target site when moved withthe target site under manual or robotic control.

In another embodiment of device 10 the system can be combined with otherdiagnostic modalities such as, but not limited to, optical coherencetomography (OCT), reflective confocal microscopy, MRI, or ultrasound toinitially localize and grossly delineate the lesion, whereupon othersurgical modalities such as, but not limited to, conventional surgery,electro-surgery, laser surgery, radiofrequency surgery, and cryosurgerycan be used to rapidly debulk the lesion as visualized by eyesight orthe above-mentioned diagnostic modalities. Dehul king is the reductionof as much of the bulk (volume) of a tumor as possible. It is usuallyachieved by surgical removal. This process would then be augmented bythe device 10 which could then remove the remaining surrounding area ofresidual anomalous tissue using resonance Raman guided laser ablation toobtain total anomalous tissue removal with a surrounding zone free ofanomalous tissue.

In another embodiment of the probe 40 or microscope 50 used in device10, there may be utilized a hollow articulated arm or waveguide such asthat used to carry an emission such as, but not limited to, infraredcarbon dioxide laser (10.6 micron) from energy source 20 T, that couldcontain ablative energy as well as the diagnostic/excitation energy fromthe source 20D as well as the scatter sensing fiber 85.

As seen in FIGS. 1 and 2, there is depicted the route by which theDiagnostic energy 20D and therapeutic energy 20 T are delivered to thetarget site 70.

Upon identification of the prospective target site 30 in tissue 120 anexciter pulse of energy such as but not limited to approximately 3.5 to7 mW of 532 nm or 785 nm energy with an on time of 1 second is producedby an appropriate laser or LED is created in the resonance Raman excitersource 20 D and is conveyed by fiber-optic 50 through lens 820. Strayenergy 825 which may be produced by the fiber-optic itself is filteredout at this point by lens filter 820. The energy produced is arrayed ina preselected pattern by the array producing device 30 as seen in FIGS.4, 5, 7 and 8. Other patterns can be produced also. The pattern is thendisplayed by the confocal microscope 50 or into the probe 50 to befocused by lens 60 onto the tissue 120 where the targeted skin 30 orother appropriate tissue is to be diagnosed and presumably treated bythe ablative laser such as but not exclusively pulsed carbon dioxidelaser, if necessary. The invention also contemplates the use of a lowenergy source of UVC radiation, to genetically modify or destroy/removeorganic micro-organisms including but not limited to viruses on or belowthe surfaces of tissues⁹. The ablative energy is carried within thelumen of cable 35DTA by fiber-optic or other suitable waveguidesurrounded by the pattern formed by the exciter 20 fibers which may beseparate from fibers that will eventually carry Raman scatter 95 to thespectrometer, or may be themselves coaxial with the Raman scatter sensorfibers. All energies with the exclusion of 825 pass through lens/filter820 In conduit 25DT Into the array forming device 30, FIGS. 1,4 and 5and thence by conduit 35DTA to the confocal

⁹ Reference 22

microscope 50 or probe 40. The exciter energy is focused and createsresonance Raman scatter 75 at the target site 70 and this scatter passesthrough filters 335 and 345 to the Sensor 80 FIG. 2. Lens 335/345 iscoated to transmit Raman scatter energy and reject any reflected exciterenergy emission trying to return as well as any ablative energy thatcould be contributing to noise. Pure Raman Scatter emission 95 isrelayed to the spectrometer 90 which then communicates by cable 105 withthe computer and database 110. Should the computer confirm the tissuefingerprint FIG. 9. to be anomalous it relays the data through conduit115 to the robotic display controller 110 or if under manual controldirectly to the ablative laser manual control 150 by fiber 155. All theconnections could be wireless. This initiates a pulse of energy from theablating laser source 20T which carries the energy in the centralportion of cable 25T by way of fiber-optic or waveguide filter 820 andthrough conduit 25 DT through or around the array forming device toprobe 40 or confocal microscope then through the focusing lens 60resulting in vaporization of the target site 70. This process isperformed repeatedly either robotically or manually under directvisualization, by visualization of the site through the monitor 130 orthrough the confocal operating microscope 50.

It can also be done by communication from the computer 100 throughconnector 115 to the robotic display controller 110, which can directthe firing of the ablating laser source 20D by cable 165Diagnosis/therapy is performed until all anomalous tissue is ablated orremoved as seen in FIGS. 7 and 8 leaving a clear tissue zonecircumscribing the perimeter of the removed anomalous tissue. Since thisinvention is at first concerned mostly with skin lesions, the preferredembodiment is: to have the exciter/sensor fibers coaxially arranged in alinear pattern as shown in FIGS. 4 and 8. Starting at the center of thevisually observed lesion FIG. 8, 120 using the array as seen in FIGS. 4,5, 7 and 8 is initiated on area 120 through the confocal microscopesystem 50, the Raman scatter is collected by the sensor fibers whereaberrant energy from the impact site is filtered by filter 335/345 andtransmitted to the sensor 80 and thence by conduit 95 to thespectrometer 90. Since all vertically arranged fibers are positive foranomalous tissue after the fingerprints FIG. 9. are adjudicated by theCPU 100, a signal is sent through the robotic controller 110 to repeatthe ablation/diagnostic episodes until the deep tissue is all clear. Theprobe is then moved toward a visually presumed periphery 210 and theprocess is repeated until by way of example area 270 is reached wherethe only positive sensor readings 250 are in the central area of theablation site 70 and at least 6 (300 microns) 260 are free of anomaloustissue.

The CPU then directs the robotic controller 110 to move the displaylaterally keeping the configuration the same as seen in FIG. 7 creatinga path of treatment around the lesion with a clear zone 200 surroundingit.

In another embodiment, fiber lasers, diode lasers, could be utilized tocreate more accurate and efficient diagnosis and therapy.

In another embodiment, a camera may be incorporated into the medicaldevice 10 to capture images of target tissue. The camera can beconventional digital or video as desired or required.

In another embodiment, LEDs of appropriate wavelength configured insimilar arrays as in FIGS. 4, 5, 7 and 8 with sensor/collector fiberscould be fitted underneath the microscope in a separate carriage (Notshown).

Seen in FIG. 8 array 260 could be used. Coaxial fibers could be usedThese fibers are arranged in a square quadratically 260 forrepresentation on the spectrometer 90 and CPU 100 They are projectedonto the perimeter of the lesion and by rasterized control by therobotic controller, by example along a track 220 either vertically orhorizontally to remove the anomalous tissue in the same manner as hasbeen described with repetitive diagnostic and ablative pulses until allanomalous tissue is vaporized as seen in FIG. 8, leaving a clear tissuezone 200 circumscribing the perimeter of the removed anomalous tissue.This process can be performed to create a clear zone FIG. 3 200enhancement of anomalous tissue grossly delineated by imaging entitiessuch as but not limited to MRI and OCT and treated with debulkingentities, such as but not limited to conventional surgery, lasersurgery, cryosurgery, electro-surgery, radiation therapy orchemotherapy. This data can be communicated by an accessory device bythe cable 135 to the CPU 100.

Different displays of fibers can be used such as but not limited toFIGS. 8 250 and 260 depending on whether the initial topography of thevisually anomalous tissue is defined from the center of the lesionoutward or from the periphery inward. Other Tracking patterns can beused, as seen but not limited to, in FIGS. 8, 250 and 260.

The pattern of the peripheral clear zone of the lesion seen in FIG. 8perimeter 210 can be saved in the computer 100, and be used by use ofthe robotic controller 110 to create a custom fitted skin graft torepair the defect created by the anomalous tissue removal.

In another embodiment of the probe 40 or microscope 50 used in device10, there may be utilized a hollow articulated arm or waveguide such asthat used to carry an emission such as, but not limited to infraredcarbon dioxide laser (10.6 micron) from energy source 20 T which couldcontain ablative energy as well as the diagnostic/excitation energy fromsource 20 D as well as the scatter sensing fiber 95. A number ofconduits and fibers could be configured to create the most efficientsystem.

In another embodiment the exciter/sensor collector fibers are separateand the therapeutic fibers or waveguide are used in a differentwavelength such as, but not limited to a high-powered pulsed carbondioxide laser energy (10.6 micron) delivered par focally to the targetsite.

In another embodiment the exciter fibers and the sensor collectionfibers are discrete within the bundle in a pattern creating an arraysuch as seen in FIGS. 5, 7 and 8.

In another embodiment, the exciter fibers and the therapeutic fibers arethe same and the sensor collector fibers are separate within conduit 85.

In another embodiment, the exciter, sensor collector, and therapeuticconduits are all separate within the bundle 35DTA.

In another embodiment, agents such as, but not limited to methyleneblue, derivatives of amino levulinic acid, talaporfin, and some preciousmetals could be given to patients to expedite diagnosis and/or treatmentshould the risk/benefit ratio warrant it.

Embodied Arrays of Diagnostic/Exciter Energy and their Usage andStrategies for Successful Treatment of Anomalous Tissue with Device 10

The goals of this invention are to remove unwanted anomalous tissue,while preserving the adjacent normal tissue. The gold standard fordetermining the difference in these two tissues has been histopatholgy.Optical biopsy with systems such as resonance Raman spectroscopy are nowcoming forward to represent a future alternative method. Up to now,regular Raman spectroscopy as well as other modes of optical biopsy havebeen unable to create the differentiation of tissues quickly enough tomake optical biopsy guided treatment of the abnormal tissues feasible.With the availability of ultrafast techniques such as but not limited toresonance Raman spectroscopy with its ability to create a fingerprint in1 second or less, the device herein 10 has become feasible. Conventionalsurgery, requires repeated histopathologic examination to determinewhether margins of anomalous tissue removal are clear of the anomaloustissue and are time-consuming and often because of location, difficultto determine, and sometimes inaccurate. Most forms of therapy that arenot performed by conventional surgery are additionally encumbered byconcerns that the modalities themselves destroy the interface betweenthe normal and abnormal tissue rendering histopathologic diagnosis ofthe anomalous tissue margin even more difficult. Herein we presentspecially designed arrays and patterns to be used in probes andprobe-like devices or microscopic delivery systems that will createanomalous tissue clear zones with non-limiting strategies for their use.All arrays can be designed with energy sources, such as but not limitedto, lasers or LEDs, and can be within or attached to either probe-likedevices such as, but not limited to dermatologic probes, bronchoscopes,laparoscopes, endoscopes, cystoscopes as well as operating microscope's,and Raman spectrometer microscopes.

The first decision needed for strategy is whether to approach theanomalous tissue to be treated from its visualized or imaged center andwork toward the surrounding normal tissue, or to create a periphery ofnormal tissue with a substantial clear zone and work toward the centerof the issue. This need be done both horizontally and in depth. Fibersarrayed in FIG. 8 in which display 250 is linear illustrates how thevertical probe pattern moves it from the center to the periphery whereit upon finding a site 270 of clear tissue begins to move by manual orrobotic control as shown in FIG. 8 to define a clear periphery 200.

Array 260 which is square and quadratic can be moved by example from thevisual periphery with DTA sites arrayed quadratically into the CPU 100for additional guidance in movement to the controller 110 into thevisible tumor mass on track 220 The arrays will then be manually orrobotically guided to remove abnormal tissue as it establishes a roughperimeter within the confines of the established visual perimeter. Itshould be noted that the array would then be adjusted to a site at theperiphery 270 where it or the 250 array would produce a new track of theperiphery 270 with a 300 Micron anomalous issue clear zone. The width ofthe clear margin desired could be a surgeon decision or a databasedecision, as would be the power, wavelength, and on time of the energysource. In some instances, where deemed feasible, this pattern of tissueremoval 210 would be stored in the database and used to create a customgraft as needed.

In an alternative embodiment, if it seems prudent, debulking of thelesion is facilitated by vision, or an imaging system such as MRI,ultrasound or other modality known in the art. Then performedsurgically, with cryotherapy, electro-surgery, radiation, or any othermodality as used in the art. Another useful embodiment of the devicewould be utilizing the arrays to guide laser therapy to discover andremove residual anomalous tissue. Varying tracking patterns would beavailable from the computer software, as well as the ability to manuallycreate tracking patterns. FIG. 8.

Provision for debulking lesions previously grossly imaged by otherimaging methods such as OCT, MRI, auto or induced fluorescence, orsimilar entities will be made utilizing the components and appropriatewave lengths, spot sizes and energy levels. Finishing areas previouslydebulked by devices such as conventional surgery, electro-surgery,cryosurgery, chemotherapy, radiation therapy, and genetic therapy, maybe performed, aided by the multi-centered super online data base 140 byconduit 135, the robotic controller 110 through conduit 115.

The invention also contemplates using resonance Raman to detect anddiagnose organic micro-organisms, including viruses (collectively“pathogens”), on a selected surface comprising a source for directingexcitation radiation at a selected surface to produce resonance Ramanscattering (RRS) representative of the pathogens; detecting means fordetecting Raman scatter at said selected surface when excitationradiation impinges on the pathogens; and

determining means for determining whether said detected Raman scatter isindicative of the presence of a pathogen sought to be diagnosed.

While the invention has been shown and described with reference tocertain embodiments thereof, it will be understood by those skilled inthe art that various changes in form and detail may be made thereinwithout departing from the spirit and scope of the invention as definedby the appended claims and their equivalents.

1. A medical device for diagnosing and eliminating or compromisingorganic micro-organisms, including viruses (collectively “pathogens”),on a selected surface comprising a first source for directing excitationradiation at a selected surface to produce resonance Raman scattering(RRS) representative of the pathogens; a second source for directing UVCradiation at the selected surface to destroy or compromise detectedpathogens; detecting means for detecting Raman scatter at said selectedsurface when excitation radiation impinges on the pathogens; determiningmeans for determining whether said detected Raman scatter is indicativeof the presence of a pathogen sought to be destroyed or compromised;activation means for activating said second source for directing UVCradiation at the pathogens issuing said Raman scatter to destroy orcompromise the pathogens only when these are determined to be thepathogens sought to be destroyed or compromised.
 2. A medical device asdefined in claim 1, wherein said excitation and UVC radiations aredelivered to said selected surface through fiber optic light conduitsarranged in a pattern to create a pathogen-free zone.
 3. A medicaldevice as defined in claim 1, wherein said excitation and UVC radiationsare delivered to said selected surface through fiber optic lightconduits arranged in a pattern to maximize efficiency of detection anderadication of pathogens.
 4. A device for detecting and eradicatingpathogens on a selected surface comprising a first source for directingan array of excitation radiation at a selected surface to produceresonance Raman scattering (RRS); a second source for directing an arrayof UVC radiation at the selected surface to irradiate pathogens at theselected surface; fiber optic or waveguide light conduits arranged in apattern to deliver said array of excitation radiation and said array ofUVC radiation to the selected surface target site; detecting means fordetecting said RRS at said target site when excitation radiationimpinges on the selected surface; and determining means for determiningwhether said detected RRS is indicative of the presence of the pathogenon the selected surface; and activation means for activating said secondsource to direct the array of UVC radiation at the selected surface toirradiate the selected surface only when the selected surface isdetermined to support or exhibit the pathogen to create a peripheralpathogen-free zone circumscribing pathogens at the selected surfacetarget site.
 5. A medical device as defined in claim 4, wherein saidfirst source emits radiation having a wavelength for producing RRS inorganic molecules including excitation radiation having a wavelengthapproximately equal to 532 nm.
 6. A medical device as defined in claim4, further comprising directing means for propagating said excitationradiation to selected portions of the selected surface.
 7. A medicaldevice as defined in claim 6, wherein said directing means includes aprobe.
 8. A device as defined in claim 6, wherein said directing meansincludes a confocal microscope.
 9. A device as defined in claim 6,wherein said fiber optic or waveguide light conduits are interposedbetween said radiation sources and said directing means.
 10. A device asdefined in claim 9, wherein said detecting means comprises a sensor forsensing said RRS and a spectrometer for analyzing said RRS to establisha detected fingerprint identifying the nature of the pathogen.
 11. Adevice as defined in claim 4, wherein said determining means comprises acomputer and a database stored on said computer containing at least onereference fingerprint associated with the pathogen, said computer beingprogrammed to compare said detected fingerprint against said at leastone reference fingerprint in said database.
 12. A device as defined inclaim 10, wherein a fiber optic conduit transmits the RRS to saidsensor.
 13. A device as defined in claim 4, further comprising a roboticcontroller programmed to repeatedly actuate said first source.
 14. Adevice as defined in claim 4, wherein said activation means includes acontroller and further comprising a robot system responding to saidcontroller and configured to move a probe or confocal microscope inrelationship to the selected surface, wherein the controller isprogrammed to repeatedly actuate said sources to emit said excitationradiation; and in, response to a control signal, emit said UVC radiationto initiate eradication of pathogens and then move either the probe orthe microscope arrays to a next successive portion of the selectedsurface.
 15. A device as defined in claim 11, wherein said computer isprogrammed to control a robotic controller to move to next adjacentareas of the targeted selected surface if the selected surface isdetermined to be pathogen-free or eradicate the pathogens on theselected surface until a pathogen-free region is detected.
 16. A deviceas defined in claim 9, wherein said fiber optic or waveguide lightconduits are arranged to form an array of optical fibers that expose apredetermined portion of the target selected surface to said UVCradiation.
 17. A device as defined in claim 6, further comprising meansfor moving said directing means over at least portions of the targetselected surface within a peripheral pathogen-free zone.
 18. A device asdefined in claim 6, wherein said directing means includes means fordirecting said radiations along tracks within said peripheralpathogen-free zone until the entire area therein has been analyzed. 19.A device as defined in claim 14, further comprising a probe or confocalmicroscope for propagating said excitation radiation to selectedportions of the selected surface at the target site and a robot systemresponding to the controller, and configured to move the probe orconfocal microscope in relationship to the selected surface, wherein thecontroller is programmed and repeatedly actuates the first source toemit the excitation radiation; and in response to a control signal,actuate the second source of the UVC energy, and then actuate the robotsystem to move the probe or the confocal microscope.
 20. A method ofdiagnosing and eradicating pathogens comprising the steps of directingan array of excitation radiation at a selected surface target site withfiber optic or waveguide light conduits arranged in a pattern to produceresonance Raman resonance RRS at said target site when excitationradiation impinges on the selected surface; and; directing an array ofUVC radiation at the selected surface target site with fiberoptic orwaveguide light conduits arranged in a pattern to destroy or compromisepathogens on the selected surface; detecting said RSS at said targetsite when excitation radiation impinges on the selected surface; anddetermining whether said detected RRS is indicative of the presence ofpathogens, whereby directing UVC eradication radiation at the selectedsurface target site to eradicate the pathogens at said selected surfaceat the target site is performed only when the selected surface targetsite is determined to exhibit pathogen to create a peripheralpathogen-free zone circumscribing a pathogen-free region at the selectedsurface target site.
 21. A method as defined in claim 20, furthercomprising using a robot system to successively move arrays of saidradiations in a programmed manner in relationship to the selectedsurface to repeatedly expose successive portions of the selected surfacewithin the peripheral pathogen-free zone to emit said excitationradiation; and in response to a control signal, emit said UVCeradication radiation and then move said arrays to a next successiveportion of the selected surface target site until the entire area withinsaid peripheral pathogen-free zone has been examined and treated.
 22. Amedical device for detecting and diagnosing organic micro-organisms,including viruses (collectively “pathogens”), on a selected surfacecomprising a source for directing excitation radiation at a selectedsurface to produce resonance Raman scattering (RRS) representative ofthe pathogens; detecting means for detecting Raman scatter at saidselected surface when excitation radiation impinges on the pathogens;and determining means for determining whether said detected Ramanscatter is indicative of the presence of a pathogen sought to bediagnosed.